Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition

Funding Source

National Institute on Minority Health and Health Disparities, Sichuan Province Science and Technology Support Program, National Institutes of Health

Grant Number

2G12MD007595, 2014SZ0071


Department of Chemistry

Document Type


Publication Date



A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 μM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 μM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility. © 2016 by the authors; licensee MDPI.


DOI: 10.3390/molecules21060771

PubMed ID: 27331805

Funding text

The authors are thankful to the Analytical and Testing Center, Sichuan University, Sichuan, China for providing analytical data, and State Key Lab of Biotherapy, Sichuan University for completing the Human Hepatoma Carcinoma Cell 7402 and 7221 activity test. This project was supported by the Science and Technology Support Program of Sichuan Province (2014SZ0071) (Shu-Fan Yin) and in part by the NIH RCMI Cancer Research Center at Xavier University of Louisiana, City, State, Country through an NIMHD Grant 2G12MD007595 (Guangdi Wang).